August2011

“Action is the foundational

key to all success. - Picasso”

In this issue...

COMMUNIQUÉ

mdi

Membrane Technologies

Ømdi Capsule FiltersØNew Technology for Large Quantity Plasmid DNA

Purification ØPharma Regulatory NewsØCompany News: mdi US officeØEvents/Seminars: mdi at Medica 2010 ØReaders Column

“scientia potentia est” (Knowledge is Power)

Welcome to the first newsletter from Advanced Microdevices Pvt. Ltd. (mdi).

mdi has been serving the Pharmaceutical and Biopharmaceutical industries as well as Life Science Research for more than 30 years. With over 15,000 products and validation services backed by integrated R&D facilities and large production capacities, mdi has been at the forefront of innovations with built-in unique performance advantages.

The Pharmaceutical and Biopharmaceutical industries are highly regulated, involve critical processes, knowledge driven and extremely competitive. Critical process owners are thus continuously looking for high quality, high performance, reliable and cost effective products, services and systems which can help them improve process efficiency and assure end product quality. There is also a strong need for technical support to not only improve efficiency but to find customized solutions to new and specific needs.

At mdi, the focus always has been to work closely with the users and to address their specif ic needs/concerns for cr it ical applications, help improve process efficiency and economics and in the process build strong interactive associations and be partners in growth. These efforts are well supported by a strong technical backup which includes problem solving, product c u s t o m i z a t i o n , r a p i d p r o t o t y p i n g , characterization and validation support, interactive technical seminars and training programs.

This newsletter is a further effort to share our knowledge and experience through technical articles, application info, regulatory news, and new product launches.

Editor

www.mdimembrane.com/newsletter

mdi Filter Selection and Scale Up SCALE UP

Microfiltration is a critical component of the formulation as well as process development exercise for any aseptic drug formulation.

As scientists are concerned about filter fluid interaction impacting the stability, purity, strength etc. of the drug product, they naturally take a keen interest in filter selection at the formulation development stage itself. Although preliminary compatibility data support initial filter selection for stability studies detailed fi lter validation studies are required to p r o v i d e e n o u g h d o c u m e n t e d evidence to justify specific filter use for these studies .

However, a critical requirement that needs to be addressed at this stage is of scalability from R&D to pilot scale to full scale production processes.

Since laboratory filtration devices with minimum membrane filter area are n o r m a l l y u s e d f o r p r o c e s s development in order to conserve p h a r m a c e u t i c a l t e s t f l u i d requirements affected by limited availability, these need to be scalable to large scale filter devices required for much larger process volumes.

o f f e r s a w i d e r a n g e o f miniaturized filter devices that are truly representative of large scale filter devices such as capsule filters and cartridge filters.

These filters, based on the filter validation studies, not only allow easily justifiable scale up to large filter devices and truly satisfy regulatory requirements, but are also ideally suited for filtrability studies with the objective to select optimal filter size, assure smoother technology transfer and maximize process efficiency.

m d i

Truly representative in terms of:

ØMaterials of construction for

different components from

the membrane filter, drainage

support layers, to the plastic

housing components and

elastomeric seals

ØFabrication processes such

as sealing methodologies etc.

ØDesign aspects such as fluid

accessibility affected by

pleated structures of large

filtration area devices

ØEnd connections for

convenience as well as to

mitigate pressure losses

associated with plumbing and

elevation

mdi Scale up Filter Devices

Large Capsule Filter

50 mm Device with 1/2” TC25mm Syringe Filter

150 cm² Capsule Filter

with 1.5” TC

2” Capsule Filter with Quick Connectors

Capsuringe

Capsule Filter

with Automatic Venting

www.mdimembrane.com/newsletter

mdi Filter Selection and Scale Up SCALE UP

Wide Range of Filter Sizes for Scale up

100ml25mm 4cm²

Filter Size Effective Filtration Area

1 Ltrs.50mm 18cm²

Volume

10 Ltrs.1” 150cm² - 260cm²

100 Ltrs.2” 500cm²

500 Ltrs.5” 1000cm²

1000 Ltrs.10” 2000cm²

2000 Ltrs.Large Capsule 6000cm²

mdi filters are available with following f i l t e r m e d i a t o m e e t v a r i e d microfiltration requirements.

ØPolyethersulfone

ØPTFE

ØNylon -66

ØPositively charged Nylon 66

ØMicro glass fibre

ØPolypropylene

Wide Range of Filter Sizes for Scale up

Capsule filters are carefully designed to encapsulate optimum filter area in small housings to ensure very low hold up volumes and maximum product recoveries.

Holdup Volumes

Ø1/4 “ Stepped Hose Barb

ؽ” Hose Barbؽ” TCØ1.5” TCØQuick ConnectorsØFemale Luer Lock inlet and

Male Luer Slip Outlet (Capsuringe)

Wide Range of End Connections

Wide Range of Membranes for Selection

100ml25mm 4cm²

Filter Size Effective Filtration Area

1 Ltrs.50mm 18cm²

Volume

10 Ltrs.1” 150cm² - 260cm²100 Ltrs.2” 500cm²

500 Ltrs.5” 1000cm²

1000 Ltrs.10” 2000cm²

2000 Ltrs.Large Capsule 6000cm²

Integrity testable with water from small 1” capsule filter to large capsule filter.

Testability

Filters to Withstand Most Common Methods of Sterilization

ØAutoclave

ØIn line steaming for cartridge filters

ØEO ØGamma Irradiation

Unique serial number on each filter and individual certificate of quality with each filter.

Traceability

Customization for Specific Needs

ØMulti-layered filters with pre-filters layers for high dirt holding capacity

ØDifferent inlet and outlet connections in the same filter

ØCapsule filter with automatic venting

mdi filters are produced by validated processes in class 10,000 clean room facilities under stringent ISO 9000:2008 quality management systems.

Quality Assurance

Certificate of Quality

Individual COQ certifying compliance to product specifications as per regulatory and industry standards

CE Certification

Filters are in conformity with the essential requirements for CE marking as per the Council Directive 93/42/EEC for Medical Devices Class - 1 published in Official Journal on 12 July 1993 (L169).

Biosafety

All materials of construction of the filters comply with the Biological

tests for Class VI plastics as described in USP 28 (88), page 2269.

USFDA CFR Title 21 Part 177.1520

Polypropylene used in the construction of these Cartridge filters is certified to comply with the USFDA CFR Title 21, Part 177.1520.

REACH Compliance

filters are manufactured using input that meet the obligation under REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) regulation (EC) No. 1907/2006 of 18 December 2006.

Non-Animal Origin

Input materials used in manufacture of filters are of vegetable/ petrochemical origin, and are free from any material of animal tissue source like cattle, sheep or goat.

mdi

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mdi

NEW TECHNOLOGY FOR LARGE QUANTITY PLASMID DNA PURIFICATION

Specialized research areas such as DNA vaccines, Gene therapy, Pharmacokinetics, automated large scale screening applications and certain diagnostic kits require large quantities of purified plasmid DNA.

Research scientists all over the world have been struggling with various issues related to large quantity plasmid DNA purification such as:

The purification time is minimized to <30 minutes giving a high purity pDNA.

The Quanta technology is scalable to provide large quantity of up to 10 mg transfection-grade plasmid DNA suitable for a variety of applications such as automated sequencing, restriction digestion, and cloning, transfection / transformation, PCR, ligation, microinjection and probe generation. mdi Quanta Mega and Giga Kits are under development.

25 Minutes Protocol

Pelleted Bacteria

Alkaline Lysis

Clear Lysate

By Filtration

Add Buffer MB

Bind/Wash

Dry

Elute

Ultra Pure Plasmid DNA

Vacuum Pump

Table top Centrifuge

Table top Centrifuge

Quanta Kits

Other Kits

Quanta Kits

Other Kits

Time (in minutes)0 30 60 90 120 150

A s p e c i a l l y d e s i g n e d microfiltration step does away with the cumbersome centrifugation / incubation processes involved in cell debris removal from the lysate.

Binding and washing steps are carried out with a c o n v e n i e n t v a c u u m manifold which does away with gravitational waiting a s s o c i a t e d w i t h conventional kits.

ØFastest pDNA isolation in <30 minutes

ØVery high binding capacities and yields in miniaturized spin columns

ØHighly concentrated pDNA: more than 1µg/µl

ØNo salt contamination due to isopropanol precipitation

ØNo yield losses due to DNA reconstitution

These kits offer numerous performance advantages over the conventional kits:

Ø

Ø?Cumbersome handling of large purification columns to get desired yields.

ØLarge elution volumes resulting in poor DNA concentration which in turn requires isopropanol precipitation and DNA r e c o n s t i t u t i o n r e s u l t i n g i n s a l t contamination and yield losses.

Ø?Time consuming 2-3 hours protocols: gravitational methods for binding, washing and elution of plasmid DNA.

A new innovative technology from mdi that helps minimize purification time and maximize yields without compromising on purity, consistency and shelf-life is now available.

These next generation Quanta Midi and Maxi prep kits from mdi for plasmid DNA purification have miniaturized midi and maxi columns with specially designed membranes which provides in 50-100 fold increase in binding capacity of a mini column. This allows low salt elution of ultrapure pDNA in as low as 200-400µl elution volume doing away with i s o p ro p a n o l p re c i p i t at i o n a n d D N A reconstitution, resulting in higher purity and yields.

0

200

400

600

800

1000

1200

Midi Kits Maxi Kits(µ

g)

Quanta Kits

Other Kits

Ø2-3 times yield

ØVacuum based binding and washing; No gravitational waiting

ØConvenient lysis and cell debris removal

Ø1/6 Process time

www.mdimembrane.com/newsletter

READERS COLUMN

MEDICA-2010, Dusseldorf

exhibited for the 12th straight year at Medica, the largest international trade fair and congress for medical technology, electro-medicine, laboratory equipments, diagnostics and drugs. The company is now credited as the best and largest producer for membranes for rapid immunoassays.

mdi

Dear Readers,

This newsletter has been introduced to initiate an interactive communication between mdi and the readers.

We would welcome and appreciate your comments and contribution to this effort.

For your comments and suggestions please contact: newsletter@mdimembrane.com

mdi

EVENTS

Advanced Microdevices Pvt.Ltd. 20-21, Industrial Area, Ambala Cantt-133006, IndiaTel : 0171-2699290, 2699471 Fax: 0171-2699221, 2699008E-mail : mdi@vsnl.com Internet : www.mdimembrane.com

PHARMA PHARMA REGULATORY NEWS

w

Chapter 62<Microbiological Examination of Non-sterile Products Tests for Specified Microorganisms>:

wNegative control is mandatory every time that the product is tested

wDelete indicative property testing of XLD agar with E.coli

wClarification to Clostridium testing

Chapter 71<Sterility Tests>:

wTerm validation has been replaced by the more appropriate term “method suitability”. This is in line with the terminology used in the tex ts on microbia l contamination of non-sterile products.

wAlternative thioglycollate medium- a reference to this alternative medium included, with the introduction of the following terms: “Where prescribed or justified and authorized”.

Negative control is mandatory every time that the product is tested

The US pharmacopeial guidelines on microbiology has been recently harmonized with EP and IP through USP 34 NF 29. These are in accordance with ICH Q4B. The highlights are:

New Office in USmdi

mdi mdi has opened its overseas business subsidiary ‘ Membrane Technologies LLC’ in USA. This is an important milestone, and will provide flexible distribution options to customers for faster product delivery. It will also address the working time difference issues and make it convenient for the customers to consult our experts during their local working hours.

It is headed by, Dr. Shreya Kanodia has over 10 years of experience in life science research. She holds a Bachelor’s degree in Biochemical Engineering from the Indian Institute of Technology, Kharagpur in West Bengal, India and a Ph.D. in Immunology/Cancer Biology from the University of Texas M. D. Anderson Cancer Center in Houston, Texas.

Contact Address Membrane Technologies LLC

555 Lakeview Rd, Ste G, Pasadena, CA 91105, Email: shreyakanodia@mdimembrane.com Phone: (626) 921-6340, Fax: (866) 634-9280

mdi

COMPANY NEWS